ORIGINAL RESEARCH ARTICLE

High myopic patients with and without foveoschisis:morphological and functional characteristics

Marcella Nebbioso . Alessandro Lambiase . Magda Gharbiya .

Alice Bruscolini . Ludovico Alisi . Vincenza Bonfiglio

Received: 6 September 2019 / Accepted: 10 April 2020

� Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract

Purpose Myopic foveoschisis (MF) is characterized

by the splitting of the retinal layers in the fovea of

patients with high myopia (HM). MF may progress

into foveal detachment or macular hole formation with

consequent loss of central vision. The aim of this study

is to investigate morphological and functional changes

of the macular region in myopic subjects with and

without foveoschisis.

Design Observational, cross-sectional, comparative

study.

Methods Forty-eight patients with HM and 24

healthy controls were evaluated by spectral domain-

optical coherence tomography (SD-OCT), multifocal

electroretinography (mfERG) and microperimetry

(MP-1) tests to assess macular thickness, functionality

and sensitivity values, respectively. The results of the

diagnostic examinations were compared between

three groups: HM patients with MF (N = 24), HM

patients without MF (N = 24) and control group (CG)

(N = 24). All statistical analyses were performed with

STATA 14.0 (Collage Station, Texas, USA). One-way

analysis of variance (ANOVA) followed by Tukey’s

post hoc test was used to analyze differences between

groups unless specified; p values\ 0.05 were consid-

ered as statistically significant. Gender distribution

was compared by the Chi square test.

Results The statistical analysis with one-way

ANOVA followed by Tukey’s post hoc test showed

a significant increase in macular thickness in HM

patients with MF when compared to both HM patients

without MF and CG. Morphological changes were

associated with functional impairment as demon-

strated by the significant decrease in amplitude of

the P1 wave and MP-1 sensitivity (p\ 0.05), accord-

ing to the anatomical landmarks.

Conclusions This study showed that the morpholog-

ical changes observed in the central retina of HM

patients with MF are associated with functional

alterations. High-tech diagnostic tests such as SD-

OCT, mfERG and MP-1 could be useful for manage-

ment in complications of MF.

Keywords High myopia � Microperimetry (MP-1) �Multifocal electroretinography (mfERG) � Myopic

foveoschisis � Pathological myopia � Retinoschisis �Spectral domain-optical coherence tomography (SD-

OCT)

M. Nebbioso � A. Lambiase (&) � M. Gharbiya �A. Bruscolini � L. Alisi

Department of Sense Organs, Sapienza University of

Rome, p. le A. Moro 5, 00185 Rome, Italy

e-mail: alessandro.lambiase@uniroma1.it

V. Bonfiglio

Department of Ophthalmology, University of Catania, Via

S. Sofia 76, 95100 Catania, Italy

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https://doi.org/10.1007/s10633-020-09767-y(0123456789().,-volV)( 0123456789().,-volV)

Introduction

The prevalence of myopia is increasing throughout the

world, becoming a prominent public health issue,

particularly in Taiwan, Japan, Hong Kong, Singapore

and the USA [1–3]. To date, myopia is one of the

ocular conditions classified as priorities by the World

Health Organization’s Global Initiative for the Elim-

ination of Avoidable Blindness [4]. High myopia

(HM), in particular, is characterized by a refractive

error greater than - 6.00 diopters (DS) and/or by an

axial length exceeding 26.5 mm [3–5]. This condition

is a major risk factor for the development of cataract,

glaucoma, retinal detachment (RD) and myopic

retinopathy [3–5]. In addition, patients with HM may

develop pathological changes of the fundus, namely

pathological myopia (PM), caused by the progressive

stretching and thinning occurring in the posterior

section of the eye [3–5]. These changes include

peripapillary intrachoroidal cavitations, choroidal

neovascular membranes, paravascular inner retinal

cysts, tractional internal limiting membrane detach-

ment, macular holes, posterior retinal detachment and

dehiscence of retinal layers (retinoschisis) [5–7].

Moreover, patients with HM and posterior staphyloma

are prone to develop myopic foveoschisis (MF), which

is characterized by the splitting of the inner foveal

layers [3–5]. In 1958, Phillips was the first to notice a

lifting of the neurosensory retina in the absence of

macular holes or RD in HM patients [8]. In 1999,

Takano and Kishi, using optical coherence tomogra-

phy (OCT) technology, objectively evaluated the

retinal status of patients with PM and confirmed

Phillips’s findings, coining the term MF [9]. Currently,

the use of spectral domain-OCT (SD-OCT) scans

allows the evaluation of morphological changes

associated with MF. It has been described that the

progressive confluence of intraretinal cysts leads to the

thickening of the MF and the accumulation of sub-

retinal fluid, which may be complicated by the

development of a macular hole, with or without RD,

and loss of central vision [10, 11]. The natural course

and progression of MF are unpredictable, mainly

because the disease is initially asymptomatic and

progresses slowly. Hence, MF is often underdiag-

nosed, and its incidence is considerably underesti-

mated. Epidemiological studies show a prevalence of

MF ranging from 9 to 34% in PM eyes [3–5, 10, 11].

Early diagnosis and monitoring of MF are crucial to

identify complications such as the development of

vitreoretinal interface traction, epiretinal membrane,

macular hole, limiting membrane detachment, par-

avascular microholes and RD [5, 10, 11]. In fact, up to

50% of highly myopic eyes with MF have been

reported to develop RD or macular hole within a few

years of diagnosis [6, 12–16].

Although many studies have investigated structural

and functional changes in myopia, few have focused

on the correlation between structural and functional

changes, especially in healthy high myopia and with

macular foveoschisis. Further on, we have also

analyzed retinal function using objective (mfERG)

and psychophysical (MP-1) tests in patients with high

myopia and macular schisis.

Therefore, the aim of this study was to evaluate

macular morphological and functional changes in

patients affected by HM. In particular, data obtained

using SD-OCT, multifocal electroretinography

(mfERG) and microperimetry (MP-1) in HM patients

with and without MF were compared with healthy

control subjects.

Materials and methods

In this study, we recruited 48 HM subjects (24 with

MF and 24 without MF) from the Retina and

Electrophysiology Unit, Department of Sense Organs,

Umberto I Policlinico of Rome. We included 24

healthy subjects as control group (CG). The research

was carried out over three months. A comprehensive

eye examination, including best-corrected visual acu-

ity (BCVA) measured using the early treatment

diabetic retinopathy study (ETDRS) charts at 4 m,

slit lamp biomicroscopy, intraocular pressure mea-

surement with Goldmann applanation tonometry,

ocular biometric measurement and dilated fundus

examination, was performed in all the subjects partic-

ipating in the study. The indications for the study and

inclusion criteria of 48 HM patients were: refractive

defect[-8.00 DS and ocular axial length[ 26 mm;

visual acuity with BCVA [ 20/50 Snellen (? 0.4

logMAR); age from 47 to 55 years; and macular

retinoschisis shown by OCT in MF group. The

exclusion criteria were: patients with B -8.00 DS;

lamellar or complete macular holes; chorioretinal

neovascularization; history of macular photocoagula-

tion; paravascular retinal cysts; cystoid macular

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edema; RD; amblyopia; glaucoma; ocular media

opacities; uveitis; chorioretinitis; neuritis; and patients

who underwent any previous ocular surgery. Were

also excluded from the study those affected by

systemic diseases that could invalidate our tests, such

as diabetes mellitus, cardiovascular disorders, cancer,

connective disease and dysthyroidism. Inclusion cri-

teria of the healthy group were: age from 48 to

55 years, BCVA [ 20/25 Snellen (? 0.1 logMAR),

refractive condition of prevalent emmetropia, no

abnormality in SD-OCT, mfERG and MP-1 exams,

and no vitreoretinal diseases, or neuritis, glaucoma,

cataract, or previous ocular surgery, etc.

One eye from each healthy subject was randomly

chosen for instrumental evaluation of the macular area

between 0 and 20 degrees, according to the anatomical

landmarks, and to the chronological order of arrival of

the participants starting from the right eye. Further-

more, 24 of the 48 patients with HM were chosen in

the absence of macular foveoschisis and 24 with

macular foveoschisis.

In accordance with the Helsinki Declaration and

Good Clinical Practice guidelines, all the patients and

controls were informed about the use of their data and

signed an informed consent. The study protocol was

approved by the Ethics Committee of the Sapienza

University of Rome.

All patients and controls were evaluated by SD-

OCT, a non-contact imaging technology that provides

a detailed cross-sectional view of the retinal profile

using an infrared laser probe and confocal scanning

laser ophthalmoscopy, mfERG, a technique that

provides an objective assessment of macular func-

tionality, MP-1 tests, a psychophysical examination

that quantifies central retinal sensitivity in different

areas and evaluates the fixation characteristics, allow-

ing the correlation of this information with the fundus.

We evaluated all three tests in one setting: retinal

sensitivity in decibel (dB) by MP-1 microperimetry;

macular thickness in micrometers (lm) by SD-OCT,

retinal function with amplitude in microvolts/squared

degree (lV/deg2) and the implicit time in milliseconds

(ms) of the P1 wave of mfERG.

OCT measurement

SD-OCT data were obtained using the Spectralis OCT

(Spectralis� HRA/OCT Heidelberg Engineering, Hei-

delberg Germany). A macular thickness map was

obtained for each eye, using the raster 25� 9 15�,25-line horizontal raster scan protocol, centered on the

fovea, with up to 10 frames averaged for each scan.

Retinal thickness and macular volume (Fig. 1) within

1 mm (central area), 3 mm (2�–5� ring) and 6 mm

(5�–10� ring) diameter area centered on the fovea -

were automatically calculated by the software

(Fig. 2). Retinoschisis on the SD-OCT images was

classified according to the extent of the outer schisis:

no macular retinoschisis, partial and/or entire macular

retinoschisis.

Electrophysiological testing

MfERG data were obtained using the Optoelectronic

Stimulator Vision Monitor MonPak 120 by Metrovi-

sion, (Perenchies, France) according to the standard

guidelines of the International Society for Clinical

Electrophysiology of Vision (ISCEV) [17]. Before

examination, pupils were dilated with tropicamide 1%

eye drops. All subjects were left to adapt to ordinary

room light for 30 min before testing. MfERG record-

ing was performed using an ERG-Jet corneal contact

lens active electrode; the cornea was previously

anaesthetized with proparacaine hydrochloride 0.5%

eye drops. A skin reference or inactive electrode was

Fig. 1 Grid used for evaluation of retinal thickness, function-

ality and sensitivity values of the macular areas using spectral

domain-optical coherence tomography (SD-OCT), multifocal

electroretinography (mfERG) and microperimetry (MP-1) tests

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placed at the outer canthus of the corresponding eye. A

ground electrode was placed on the patient’s earlobe.

The active, inactive and ground electrodes were

connected with a junctional box, from which signals

were delivered to additional recording components for

amplification and display. MfERG was evaluated on

the computerized Optoelectronic Stimulator (Table 1)

[17]. The standard display was a hexagonal stimulus

pattern scaled in size to produce mfERG responses of

approximately equal amplitude across the healthy

retina. Roughly half of the elements were illuminated

at any one time. Thus, the central hexagons were

smaller than the more peripheral ones. The stimulus

field consisted of a hexagonal array with the fixation

point at the center. The field contained either 61

hexagons within a diameter of 20�–25� radius from the

fixation point to edge of display. Amplitudes and

implicit times of three peaks named N1, P1 and N2

were extrapolated using the first-order Kernel. The

average responses were over a group of up to three

rings from zero to 10 degrees of eccentricity relative to

fixation (Fig. 3a). The P1 peak includes the activity of

the cells contributing to the light-adapted b-wave and

oscillatory potentials of the full-field ERG [17].

Perimetric examinations with MP-1

MP-1 was performed in a dedicated psychophysics

dark room. All subjects had a pupil diameter wider

than 4 mm, required for the MP-1 Nidek measurement

(Nidek Technologies Padua, Italy). A Goldmann III

size white stimulus with a luminance of 1.0 cd/m2 and

duration of 200 ms was projected onto a white

background. The stimulus intensity ranged from 0 to

34 dB, and the light threshold was determined by a

4–2 staircase strategy. The MP-1 test is based on a 4–2

full threshold staircase strategy using a Goldmann III

stimulus size. The measured test points in the MP-1

are shown in Fig. 3b. The fixation target is a 1�diameter red circle, and the background luminance is

set at 31.4 asb. The maximum luminance of the MP-1

is 10,000 asb, and the stimulus dynamic range is

Fig. 2 Patient X.Y. with high myopia (HM) and foveoschisis.

Spectral domain-optical coherence tomography (SD-OCT)

shows macular schisis and outer retinal layer dehiscence in the

fovea (white arrow). The topographic retinal map of the SD-

OCT reveals localized retinal elevation in the area of

foveoschisis. Bruch’s membrane (BM), internal limiting mem-

brane (ILM)

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between 0 and 34 dB. Only reliable visual fields were

used in the analyses, defined as a fixation loss (FL) rate

\ 20% and a false-positive (FP) rate \ 15%. Using

the retinal sensitivities obtained, the mean sensitivity

in the fovea, within 2 degrees, 2–5 degrees and 5–10

degrees were calculated. To assess fixation stability,

movements of the fundus were tracked during the

examination while the patient stared at the fixation

target.

Statistical analysis

Statistical analysis was performed using the STATA

14.0 (Collage Station, Texas, USA). Results were

presented as mean value ± SD. One-way analysis of

variance (ANOVA) followed by Tukey’s post hoc test

was used to analyze differences between groups unless

specified. The ANOVA test was also used to compare

mean age between study groups. Gender distribution

was compared by the Chi square test; p values\ 0.05

were considered as statistically significant.

Results

In the present study, we enrolled 48 eyes of 48 HM

patients with a mean age of 54.1 ± 2.3 years (ranging

from 47 to 55 years). Twenty-four HM eyes with MF

had a mean refractive error of - 14.23 DS and a mean

BCVA of 20/40 Snellen or ? 0.3 logarithm of the

minimum angle of resolution (logMAR). An addi-

tional group of 24 HM patients without foveoschisis

was included. They had a mean refractive error of

- 12.09 DS, and a mean BCVA of 20/20 (0.0

logMAR). Twenty-four healthy, emmetropic subjects

were also included as the control group (CG), they had

a mean age of 53.2 ± 1.9 years SD (ranging from 48

to 54 years of age) and a mean BCVA of 20/20 (0.0

logMAR). We checked for the normality of our data

and ANOVA assumptions were tested and met. The

mean age and gender distribution between the three

groups was not statistically significant (p values

\ 0.05).

We examined a 10� macular area with SD-OCT,

mfERG and MP-1 to assess macular thickness,

amplitude and implicit time of the P1 wave and retinal

sensitivity. No abnormality in SD-OCT, mfERG and

Table 1 Type of analysis of multifocal electroretinography (mfERG)

Six minutes per analysis MfERG photopic response 61B

Optical correction As required at 30 cm

Stimulated fields Thirty degrees horizontally and 23 degrees vertically

Modes of stimulation and

zones

Areas covering the central 25� of the retina and scaled eccentrically to simulate an array of 61

hexagons. Zones of size 3.4� centrally

Hexagons modulated Between a high luminance of stimulations set at 200 cd/mq for the bright flashes and 1 cd/m2 for the

dark flashes according to a binary pseudo-random m-sequence

Standard stimulation Black/white monochrome cathode ray tube monitor with blue

Background: rod and cone responses

Frame frequency 120 Hz to provide higher temporal resolution

Band-pass filtering High pass cutoff 10 Hz; low pass cutoff 300 Hz; amplified with a gain of 100,000

Stimulus screen Surrounded by uniformly illuminated background cover with a luminance set at 30 cd/m2 to

eliminate the rod responses

Stimulus frequency Set at 17 Hz to optimize the amplitude of responses

Fixation stability Monitored with an infrared refractor camera

Cutoff of amplitude P1-N1 in

lV/deg2

Ring 1: 104; Ring 2: 78; Ring 3: 57.6; Ring 4: 42.9; Ring 5: 41.7

Parameters used on the computerized Optoelectronic Stimulator Vision Monitor MonPack 120 Metrovision (Perenchies, France). The

analysis generates a histogram for each of the extended zones indicating the average amplitude of the peaks, and of the root mean

square (RMS) in microvolts/deg2 (lV/deg2). The RMS characterizes the energy content of each response. Several visualization

modes were obtained with 2-D and 3-D maps. Different types of ring display allow the measurement of P1–N1 amplitude and implicit

time, which can be compared to normative data to evaluate the general size and timing of signals in a given patient

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MP-1 examinations was recorded in the CG. In HM

patients with MF, SD-OCT showed an increase in

macular thickness (Fig. 2) associated with a reduction

in the amplitude and a delay in the implicit time of the

P1 wave recorded by mfERG. Lower values of retinal

sensitivity, as assessed by MP-1, were also found in

these subjects (Fig. 3).

Patients with MF showed an increased macular

thickness, assessed by SD-OCT, when compared with

both the HM patients without MF and the CG

(ANOVA, p\ 0.001) (Table 2). The morphological

changes observed in patients with MF were associated

with a functional impairment as demonstrated by the

decreased P1 wave amplitude evaluated by mfERG

(p\ 0.001) (Table 2), and the decreased macular

sensitivity in the three areas assessed with MP-1

(ANOVA, p\ 0.001) (Table 2). The values of

implicit time in the mfERG were statistically signif-

icant only between 5� and 10� (Table 2). Furthermore,

HM and CG did not show significant difference, in the

variables analyzed, except for the third ring of SD-

Fig. 3 Patient X.Y. the figure shows lower values of retinal

functionality with delay in the implicit time and reduction in the

amplitude of the mfERG P1 waves registered in the area affected

by myopic foveoschisis (MF) (a). P1 average waveform and

standard deviation (±) of amplitude (A) and implicit time

(T) from the three rings (1, 2 and 3). These values indicate that

the patient responses are reduced. The microperimetry (MP-1)

shows lower values of retinal sensitivity in the same area as well

(b)

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OCT and the mfERG amplitude in all the rings

(Table 2).

Discussion

The purpose of our study was to evaluate the

morphological and functional retinal changes in

patients affected by HM with and without MF using

SD-OCT, mfERG and MP-1. We demonstrated that

significant retinal functional changes occur in MF

subjects with SD-OCT anatomical alterations. To the

best of our knowledge, we evaluated two groups of

patients with HM, those affected and not affected by

macular foveoschisis [18]. Moreover, the decreased

sensitivity to MP-1 tests, probably related to the

stretching of the photoreceptor outer segments, is also

useful in the evaluation of myopia-related retinal

foveoschisis. Several studies have been carried out to

describe MF in HM patients; however, functional

changes associated with the morphological character-

istics of these subjects have not yet been reported. In

1938, Rochon-Duvigneaud observed a histological

description of foveoschisis in a highly myopic eye that

appears to be very similar to our SD-OCT results [19].

Using OCT scans, it has been clearly demonstrated

that MF in PM patients is characterized by a detach-

ment of the neuroretina at the level of the plexiform

layer [19, 20]. It has been hypothesized that the main

causes of retinal delamination in myopic macular

retinoschisis could be the posterior myopic staphy-

loma, and incomplete vitreous detachment that exerts

excessive traction on a previously stretched posterior

pole [12, 14, 21]. It has been also demonstrated that the

presence of vitreous pre-retinal membranes represents

a risk factor for MF progression, while the role of axial

Table 2 Data obtained using spectral domain-optical coher-

ence tomography (SD-OCT), multifocal electroretinography

(mfERG), and microperimetry (MP-1) in high myopia (HM)

patients with and without myopic foveoschisis (MF) compared

to the control group (CG)

Area MF SD-OCT

mean ± SD

HM SD-OCT

mean ± SD

CG SD-OCT

mean ± SD

p

ANOVA MF versus

HM*

MF versus

CG*

HM versus

CG*

2� 406.29 ± 25.59 276.08 ± 8.33 271.32 ± 9.61 \ 0.001 \ 0.001 \ 0.001 NS

2�–5� 420.19 ± 41.01 342.70 ± 19.92 300.87 ± 10.01 \ 0.001 \ 0.001 \ 0.001 NS

5�–10� 382.10 ± 12.09 298.11 ± 6.04 283.48 ± 8.68 \ 0.001 \ 0.001 \ 0.001 \ 0.001

MF mfERG A HM mfERG A CG mfERG A

2� 51.24 ± 15.01 90.33 ± 19.61 155.21 ± 8.08 \ 0.001 \ 0.001 \ 0.001 <0.001

2�–5� 31.00 ± 12.71 59.32 ± 8.00 89.91 ± 2.81 \ 0.001 \ 0.001 \ 0.001 <0.001

5�–10� 29.91 ± 10.00 40.30 ± 4.51 61.29 ± 2.99 \ 0.001 \ 0.001 \ 0.001 \ 0.001

MF mfERG T HM mfERG T CG mfERG T

2� 44.21 ± 2.98 44.05 ± 3.02 44.39 ± 3.09 NS NS NS NS

2�–5� 46.08 ± 7.31 39.89 ± 2.09 41.89 ± 2.01 NS NS NS NS

5�–10� 45.68 ± 4.01 42.05 ± 1.97 42.11 ± 3.09 \ 0.05 \ 0.05 \ 0.05 NS

MF MP-1 HM MP-1 CG MP-1

2� 11.90 ± 3.15 19.11 ± 2.03 20.00 ± 0.00 \ 0.001 \ 0.001 \ 0.001 NS

2�–5� 12.09 ± 2.90 19.09 ± 1.09 19.04 ± 1.20 \ 0.001 \ 0.001 \ 0.001 NS

5�–10� 12.31 ± 2.99 18.08 ± 1.06 19.00 ± 1.30 \ 0.001 \ 0.001 \ 0.001 NS

A one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test was applied for analysis of differences between groups.

Macular area thickness (in lm) through SD-OCT. Retinal functional amplitude (A) expressed as microvolts/deg2 (lV/deg2) and

implicit time (T) in milliseconds (ms) of the P1 wave with mfERG. Retinal functionality expressed as sensitivity values in dB

measured by MP-1

Values are expressed as mean ± standard deviation (SD). The statistical significance was attested at a probability of p\ 0.05. Value

significantly higher by one-way ANOVA and Tukey’s post hoc test (in bold)

NS not significant

*After Tukey correction

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length and chorioretinal atrophy in the progression of

the disease has not been clearly established yet

[9, 22–26].

Polito et al. and Lai et al. reported some cases of

foveoschisis with incomplete vitreous detachment that

recovered after vitreo-retinal adhesion release with

increased visual function and normalization of OCT

scans. This observation supports the hypothesis that an

incomplete vitreous detachment, with less severe

traction on the retina, may represent a cause of MF

in highly myopic eyes, which could resolve sponta-

neously [26, 27]. Shimada et al. investigated morpho-

logical changes occurred during the development of

early RD in HM patients with MF performing a series

of OCT scans in five patients. This longitudinal

research highlighted that the progression from MF to

RD goes through four stages, and the formation of an

outer lamellar hole predisposes to RD [9]. In addition,

Lai et al. found that foveal detachment can also

spontaneously resolve in patients with high myopic

traction maculopathy without evidence of posterior

vitreous detachment [27].

In our study, we evaluated retinal function and

morphological changes in patients with HM and MF

through three hi-tech examinations, SD-OCT, mfERG

and MP-1. We demonstrated that the macular central

area in highly myopic eyes affected by MF showed

functional alterations associated with anatomical

changes. These findings are in line with previous

studies showing retinal thickening at the posterior pole

and separation between the less reflective external

retina and the more reflective internal one, in HM

patients with MF [9, 14, 20, 22–26].

Notably, in our research, MF was mainly confined

to the 10� scanning area, and no disruption of any

detached internal limiting membrane was noted.

Nevertheless, the macular sensitivity analysis per-

formed by mfERG and MP-1 detected a significant

alteration of the retinal function in patients with HM

and MF. Previous studies demonstrated that

microperimetry shows an adequate reproducibility,

greater than conventional perimetry, to evaluate mean

retinal sensitivity in patients with macular diseases

[28]. Sugiura et al. showed that retinal sensitivities,

measured by microperimetry, declined with the

increase in retinal thickness, assessed by SD-OCT

[28]. In addition, Park and colleagues showed that,

especially in patients with HM, the correlation

between structural (thickness) and functional

(amplitude/implicit time) changes should be consid-

ered when interpreting retinal structure and function

using SD-OCT and mfERG [10].

In our study, in order to minimize the impact of age

on the results, only subjects aged between 47 and

55 years were included. Moreover, it is well known

that mfERG can be used for the quantitative and

objective detection of abnormal macular areas [29]. In

fact, the first-order kernel mainly reflects the function

of the outer retina, especially of the cones [29]. The

differences of P1 implicit time among the three groups

of patients were statistically significant in ring 5�–10�,but only for HM patients with MF versus HM patients

without MF, and HM patients with MF versus CG. We

can therefore assert that amplitude of the mfERG is

more sensitive than implicit time. The reasons for the

increased macular thickness caused by the schisis

associated with the thinning in the retinal morpholog-

ical profile (SD-OCT) and the decreased retinal

sensitivity (mfERG/MP-1) are probably related to

the stretching of the photoreceptor outer segments.

The phenomenon of abnormal axial elongation could

explain the enlargement of the subretinal space with

consequent decreased foveal cellular density caused

by ischemia and retinal circulation disturbances [10].

In our study, we described a positive correlation

between TROL in retinal macular areas and mfERG

and MP-1 tests. Consequently, a thicker retina outer

layer may imply an improved photoreceptor metabo-

lism and better visual function, as also demonstrated in

another study using mfERG and SD-OCT [30]. There

are two key pathological factors that are deemed to be

responsible for this retinal dysfunction. One is the

mechanical stretching related to posterior staphyloma

and vitreous traction of the inner retina associated with

the elongation of the globe in myopic eyes. The other

is the metabolic distress of the photoreceptor layer

caused by a decrease in blood supply of the thinned

HM choroid [30]. Ultimately, both the mechanical and

vascular factors may contribute to the derangements of

the retinal functional responses [15].

It has also been suggested that other factors, such as

the dysfunction of the dopaminergic system, may play

a role in the pathogenesis of the functional decline in

myopic eyes [30, 31]. Experimental studies in animal

models have demonstrated that an increase in retinal

levels of dopamine activates D1 and D2 dopaminergic

receptors present throughout the retina generating a

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signal that inhibits axial growth once the eye has

reached a normal length [31–34].

Currently, OCT scans and BCVA are the most

commonly used tools to define MF progression,

especially because of the lack, in many clinics, of

more sophisticated techniques such as MP-1 and

mfERG [9, 14]. Nevertheless, the clinical work-up and

follow-up of HM patients with MF should include hi-

tech diagnostic tests such as SD-OCT, mfERG and

MP-1, which could be useful not only for the detection

of macular modifications in MF, but also to assess the

relationship between functional variations and struc-

tural degeneration. These methods may allow predict-

ing the disease’s progression providing, especially in

the presence of complications, an objective basis for

the management of surgical treatment and the pre-

vention of loss of sight in MF patients. In order to fully

understand the processes involved in retinal damage, a

further study aiming to longitudinally evaluate the

results of these examinations in a larger population of

HM patients with MF will be carried out at our clinic.

Funding No funding was received for this research.

Compliance with ethical standards

Conflict of interest All authors certify that they have no

affiliations with or involvement in any organization or entity

with any financial interest (such as honoraria; educational

grants; participation in speakers’ bureaus; membership,

employment, consultancies, stock ownership or other equity

interest; and expert testimony or patent-licensing arrangements)

or non-financial interest (such as personal or professional rela-

tionships, affiliations, knowledge or beliefs) in the subject

matter or materials discussed in this manuscript.

Statement of human rights All procedures performed in

studies involving human participants were in accordance with

the ethical standards of the institutional and/or national research

committee and with the 1964 Helsinki Declaration and its later

amendments or comparable ethical standards.

Statement on the welfare of animals No animals were used

in this research.

Informed consent Informed consent was obtained from all

individual participants included in the study.

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